Autism and Pervasive Developmental Disorder

Dr. Weyrich's Naturopathic Functional Medicine Notebook

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Etiology

Autism appears to have a multifactorial origin, and the separation of various factors that are associated with the incidence of autism into cause and effect is far from clear.

For example:

Yeast overgrowth in the GI tract is very commonly associated with autism, and symptoms often abate when the yeast infection is cleared.
High body burdens of mercury are also often associated with autism, and symptoms often abate when the mercury burden is cleared.
But it has also been observed that yeast overgrowth increases the absorption of mercury from the environment.
Does that mean that yeast infection causes mercury toxicity?
On the other hand, it has also been observed that it is harder to clear a yeast burden without first clearing a coexisting mercury burden.
Does this mean that mercury toxicity causes yeast overgrowth?
Or do we have a positive feedback cycle in which each reinforces the other?
Just to muddy the water further, childhood vaccines have historically contained high levels of mercury (used as a preservative), and there are also reports suggesting that administering certain vaccines while a child has a yeast overgrowth is associated with the onset of autism.

Therefore with the caveat that association does not necessarily distinguish between cause and effect, the following factors have been associated with autism, in no particular order:

High incidence of otitis media (ear infections) [Kontstantareas1987]. This may be associated with hearing impairment or to yeast dysbiosis secondary to antibiotic treatment [Shaw2008].
Elevated urinary levels of 3-hydroxyphenyl-3-hydroxypropionic acid (HPHPA) and other markers of dysbiotic overgrowth with Clostridia spp. are common in autism [GP].
Elevated urinary levels of arabinose, which may be problematic for children with a defect in their metabolism of pentose sugars. High levels of arabinose are found in certain fruits (apples and pears), but also arise from dysbiotic overgrowth of yeast [Shaw2008].
Toxic metal exposure (mercury, lead, etc.) [Shaw2008].
Gastrointestinal abnormalities observed by Andrew Wakefield (Royal Free Hospital, London) and Karoly Hovarth (University of Maryland School of Medicine) after vaccination with certain types of measles vaccine [Shaw2008].
Genetic diseases of purine metabolism reported by Ted Page, Mary Coleman, et al [Shaw2008].
MMR (Measles, Mumps, Rubella) vaccine. The British gastroenterologist Andrew Wakefield has associated lymphoid hyperplasia of the gastrointestinal tract leading to fecal impaction with the MMR vaccine [Shaw2008].
DPT (Diphtheria, Pertussis, Tetanus) vaccine [Bolte1998].
Hepatitis B vaccine [Shaw2008].

Diagnosis

Dysbiosis (Organic Acid Test)

Differential Diagnosis

Generally speaking, insurance companies are more likely to reimburse for treatment of underlying organic disorders than they are for autism itself. Hence it is particularly important to identify and document any underlying organic disorders that may be associated with or cause autistic behavior. Consider the following:

Heavy metal toxicity.
Gut dysbiosis.
Genetic defect in purine metabolism [Shaw2008].
Genetic defect in pentose sugar metabolism [Shaw2008].
Vitamin B12 deficiency [stuart2006].

Note however that insurance companies are reluctant to pay for the tests required to diagnose some of these underlying organic disorders, because a direct linkage between autism and these disorders has not yet been established to the satisfaction of the insurance companies.

Treatment

Treat dysbiosis with appropriate antifungal or antibiotic agents, as indicated by the Organic Acid Test.
Reduce the risk of recurrent dysbiosis by adding probiotics and prebiotics to diet and by controlling intake of simple carbohydrates (sugars etc.) that feed yeast.
Diagnose and treat any underlying inborn errors of metabolism, using vitamins, minerals, and dietary protocols as appropriate.
Implement other dietary modifications based on food sensitivities.

Hypotheses

Arabinose

It is not clear whether elevated urinary levels of arabinose detected in by the Organic Acid Test" are simply a marker for yeast dysbiosis, or are pathogenic in their own right.

In some cases, it appears that a metabolic defect in the processing of pentose sugars such as arabinose may be the cause, since it is reported that in some children, eating fruits rich in arabinose (apples and pears) rapidly induces an exacerbation of autistic symptoms [Shaw2008].

It has also been hypothesized that arabinose, being an aldol (reducing) sugar which contains an aldehyde functional group, may contribute to pathology by reacting with the terminal ammonia group of the amino acid lysine, which is found in many proteins of the body, to form a pentosidine, which may further react with an arginine in an adjoining protein strand to form a pentosine link [Shaw2008, pg 36]. The pentosidine link alters the structure and function of the affected proteins, which may be enzymes.

Dr. Weyrich notes that this is similar to the mechanisms underlying protein glycosylation, which is measured by the hemoglobulin-A1C test [Sell1989]. Both protein glycosylation and formation of pentosine links are associated with aging - once these links are formed, they persist until the cell they are associated with dies and is replaced. Note that neurons are not replaced when they die. The concentration of pentosidines has been reported to increase linearly with age [Sell1989].

Elevated protein-bound arabinose has been found in the serum proteins of schizophrenics and in children with conduct disorders [Varma1983] [Varma1980]. Dr. Weyrich notes that it is not clear whether this is a marker for elevated arabinose, or a cause of the neurological pathology. In any case, accelerating the aging process is not a good thing.

Elevated urine arabinose has also been found in an autistic child in whom a brain MRI showed diffuse demyelination [Shaw2008].

ICD-9 Codes

ICD9-Code	Description	Comments

References

Unless specifically noted above, references used in the construction of this web page include the following:

[FDM] Lecture notes from Functional Medicine University.

[SCNM] Lecture notes from Southwest College of Naturopathic Medicine.

[UT] Lecture notes from the University of Tennessee graduate programs in Chemistry and Biochemistry.

[Shaw2008] Shaw W. Biological Treatments for Autism & PDD, Third Edition. (2008).

[Kontstantareas1987] Konstantareas MM, Homatidis S. Ear infections in autistic and normal children. J Autism Dev Disord. 1987 Dec;17(4):585-94.

[Bolte1998] Bolte ER. Autism and Clostridium tetani. Med Hypotheses. 1998 Aug;51(2):133-44. Review.

[Sell1989] Sell DR, Monnier VM. Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. J Biol Chem. 1989 Dec 25;264(36):21597-602.

[Varma1983] Varma R, Michos GA, Gordon BJ, Varma RS, Shirey RE. Serum glycoconjugates in children with schizophrenia and conduct and adjustment disorders. Biochem Med. 1983 Oct;30(2):206-14.

[Varma1980] Varma R, Hoshino AY. Serum glycoproteins in schizophrenia. Carbohydr Res. 1980 Jul;82(2):343-51.

[Stuart2006] J.J. Stuart & S.M. Pacholok. Could it be B12? An Epidemic of Misdiagnoses. Sanger, CA: Quill Driver Books/Word Dancer Press (2006).

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This web page is http://www.DrWeyrich.com/disorders/autism.html - Phone Dr. Weyrich at (480) 423-6952